Bipolar Disorder is a common, often severe mental illness. Family, twin, and adoption studies have demonstrated that genes are the major determinant of individual risk for the disorder, but as in other common disorders, the identification of these genes has proven to be a significant challenge. In collaboration with 10 academic centers across the United States, we have recruited a large sample of families in which at least 2 siblings suffer from bipolar disorder or related mood disorders. This is the largest sample ever to participate in a genetic study of bipolar disorder. All research participants have undergone a diagnostic interview and provided a blood sample for DNA analysis. Genetic linkage studies have been performed using molecular markers evenly spaced across all chromosomes. These studies suggest that regions on chromosomes 6, 8, 13, 17, 18, and 22, among others, may contain genes that contribute to bipolar disorder in these families. Ongoing work is aimed at identifying the actual genes involved. Using the latest genotyping chip technology and DNA pooling, we performed and conducted the first genome-wide association study of bipolar disorder. The results implicated several genes, each of small effect, suggesting that bipolar disorder is a polygenic disease. Ongoing work is aimed at correlating our results with those of other genome-wide association studies and studying the genes that seem to play the biggest role in disease risk.